The specific objectives of this project are to design and synthesize the following: 1. Congeners of lead compounds having confirmed activity, to enhance activity or potency. 2. Prodrugs with structural modifications that may provide improved pharmacokinetics, altered drug transport, improved bio-availability through increased water solubility, or increased chemical stability. 3. Other altered structures that possess elements of both congener and prodrug. Modifications of a lead may also include partial structures. 4. Compounds related to natural products, e.g., such as alkaloids, heterocycles, nucleosides, peptides.